9-133990287-C-T

Variant names:

• chr9-133990287-C-T
• rs10993884
• NM_001134398.2:c.204+1788G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001134398.2(VAV2):​c.204+1788G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.269 in 152,066 control chromosomes in the GnomAD database, including 6,065 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.27 (6065 hom., cov: 32)
• Consequence: VAV2 NM_001134398.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.134
• Publications: 1 publications found

Genes affected

VAV2 (HGNC:12658): (vav guanine nucleotide exchange factor 2) VAV2 is the second member of the VAV guanine nucleotide exchange factor family of oncogenes. Unlike VAV1, which is expressed exclusively in hematopoietic cells, VAV2 transcripts were found in most tissues. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.323 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VAV2	NM_001134398.2	c.204+1788G>A		intron_variant	Intron 1 of 29	ENST00000371850.8	NP_001127870.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VAV2	ENST00000371850.8	c.204+1788G>A		intron_variant	Intron 1 of 29	1	NM_001134398.2	ENSP00000360916.3
VAV2	ENST00000406606.7	c.204+1788G>A		intron_variant	Intron 1 of 26	1		ENSP00000385362.3
VAV2	ENST00000371851.1	c.204+1788G>A		intron_variant	Intron 1 of 27	5		ENSP00000360917.1
VAV2	ENST00000486113.1	n.185+1788G>A		intron_variant	Intron 1 of 2	2

Frequencies

GnomAD3 genomes AF: 0.269 AC: 40855 AN: 151946 Hom.: 6066 Cov.: 32

Gnomad AFR AF: 0.183

Gnomad AMI AF: 0.410

Gnomad AMR AF: 0.251

Gnomad ASJ AF: 0.327

Gnomad EAS AF: 0.128

Gnomad SAS AF: 0.167

Gnomad FIN AF: 0.332

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.327

Gnomad OTH AF: 0.308

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.269 AC: 40862 AN: 152066 Hom.: 6065 Cov.: 32 AF XY: 0.268 AC XY: 19907 AN XY: 74330

African (AFR) AF: 0.183 AC: 7601 AN: 41496

American (AMR) AF: 0.251 AC: 3837 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.327 AC: 1136 AN: 3470

East Asian (EAS) AF: 0.128 AC: 661 AN: 5168

South Asian (SAS) AF: 0.167 AC: 803 AN: 4818

European-Finnish (FIN) AF: 0.332 AC: 3511 AN: 10588

Middle Eastern (MID) AF: 0.401 AC: 118 AN: 294

European-Non Finnish (NFE) AF: 0.327 AC: 22179 AN: 67914

Other (OTH) AF: 0.305 AC: 643 AN: 2108

Alfa AF: 0.241 Hom.: 963

Bravo AF: 0.259

Asia WGS AF: 0.168 AC: 582 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.1
DANN	Benign	0.65
PhyloP100		-0.13
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10993884; hg19: chr9-136855409;